Detection of disordered breathing

ABSTRACT

Devices and methods for detecting disordered breathing involve determining that the patient is asleep and sensing one or more signals associated with disordered breathing indicative of sleep-disordered breathing while the patient is asleep. Sleep-disordered breathing is detected using the sensed signals associated with disordered breathing. The sensed signals associated with disordered breathing may also be used to acquire a respiration pattern of one or more respiration cycles. Characteristics of the respiration pattern are determined. The respiration pattern is classified as a disordered breathing episode based on the characteristics of the respiration pattern. One or more processes involved in the detection of disordered breathing are performed using an implantable device.

RELATED PATENT DOCUMENT

This application is a division of U.S. patent application Ser. No.10/309,770 filed on Dec. 4, 2002, and issued as U.S. Pat. No. 7,252,640which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to detecting disorderedbreathing, including sleep and non-sleep disordered breathing.

BACKGROUND OF THE INVENTION

Sleep is generally beneficial and restorative to a patient, exertinggreat influence on the quality of life. A typical night's sleep for anormal person begins with a sleep stage known as slow wave sleep (SWS)characterized by low frequency electroencephalogram (EEG) activity. Asthe person falls asleep, brain activity declines and there is aprogressive increase in the depth of sleep. At approximately ninetyminute intervals, sleep lightens and a sleep stage known as rapid eyemovement (REM) sleep is initiated. REM sleep is characterized by highfrequency EEG activity, bursts of rapid eye movements, skeletal muscleatonia, and heightened autonomic activity.

There are typically 4-6 REM periods per night, with increasing durationand intensity toward morning. While dreams can occur during either REMor SWS sleep, the nature of the dreams varies depending on the type ofsleep. REM sleep dreams tend to be more vivid and emotionally intensethan SWS sleep dreams. Furthermore, autonomic nervous system activity isdramatically altered when REM sleep is initiated.

In patients with respiratory or heart disease, the brain during sleepcan precipitate breathing disturbances, myocardial ischemia, orarrhythmia. Although REM sleep is a necessary component of normal sleep,serious consequences may be associated with both the increase inautonomic activity and the intense emotional responses that accompanydreaming in patients with cardiovascular disease or respiratorydisorders, for example.

Disruptions of the respiratory system during sleep may include theconditions of sleep apnea or sleep hypopnea. Sleep apnea is a seriousbreathing disorder caused by airway obstruction, denoted obstructivesleep apnea, or derangement in central nervous system control ofrespiration, denoted central sleep apnea. Regardless of the type ofapnea, people with sleep apnea stop breathing repeatedly during theirsleep, sometimes hundreds of times a night and often for a minute orlonger. Whereas sleep apnea refers to cessation of breathing, hypopneais associated with periods of abnormally slow or shallow breathing. Witheach apnea or hypopnea event, the person generally briefly arouses toresume normal breathing. As a result, people with sleep apnea orhypopnea may experience sleep fragmented by frequent arousals.

An adequate quality and quantity of sleep is required to maintainphysiological homeostasis. Prolonged sleep deprivation or periods ofhighly fragmented sleep ultimately will have serious healthconsequences. Chronic lack of sleep may be associated with variouscardiac or respiratory disorders affecting a patient's health andquality of life.

SUMMARY OF THE INVENTION

Various embodiments of the present invention involve detectingdisordered breathing including sleep apnea and hypopnea. In oneembodiment of the invention, a method for detecting disordered breathinginvolves determining that the patient is sleeping and sensing one ormore signals indicative of disordered breathing while the patient isasleep. Disordered breathing is detected using the one or more sensedsignals. At least one of determining the patient is asleep, sensingsignals while the patient is asleep, and detecting disordered breathingis performed at least in part implantably.

In another embodiment of the invention, a method for detectingsleep-disordered breathing involves detecting respiration patterns ofone or more respiration cycles. One or more characteristics of therespiration patterns are determined. The respiration patterns areclassified as disordered breathing based on the characteristics of therespiration patterns.

Another embodiment of the invention includes a device for detectingsleep disordered breathing comprising a sensor system configured tosense one or more signals indicative of disordered breathing. The devicealso includes a sleep detector configured to determine that a patient isasleep. The device further includes a disordered breathing detectorcoupled to the sensor system and the sleep detector. The disorderedbreathing detector is arranged to detect disordered breathing based onan output of the sleep detector and the one or more signals indicativeof sleep disordered breathing. At least one of the sensor system, thesleep detector, and the disordered breathing detector uses animplantable device.

A further embodiment of the invention includes a sleep-disorderedbreathing detection device comprising a sensor system configured todetect a respiration pattern of one or more respiration cycles. Thedevice further includes a detector system coupled to the sensor system.The detector system is configured to determine one or morecharacteristics of the respiration pattern and classify the respirationpattern as disordered breathing using the one or more characteristics ofthe respiration pattern. At least one of the sensor system and thedetector system uses an implantable device.

Another embodiment of the invention involves a system for detectingdisordered breathing including means for determining that the patient isasleep, means for sensing, while the patient is asleep, one or moresignals indicative of disordered breathing, and means for detectingdisordered breathing based on the one or more sensed signals, wherein atleast one of the means for determining, means for sensing, and means fordetecting uses an implantable device.

In yet another embodiment of the invention, a sleep-disordered breathingdetection system includes means for detecting a respiration pattern ofone or more respiration cycles, means for determining one or morecharacteristics of the respiration pattern, and means for classifyingthe respiration pattern as sleep-disordered breathing based on the oneor more characteristics of the respiration pattern, wherein at least oneof the means for detecting, means for determining, and means forclassifying uses an implantable device.

Another method for detecting disordered breathing in a patient inaccordance with an embodiment of the invention includes detecting arespiration pattern of one or more respiration cycles. Characteristicsof the respiration pattern are determined and the respiration pattern isclassified as disordered breathing based on the characteristics. Atleast one of detecting, determining, and classifying is performed atleast in part implantably.

Another embodiment of the invention includes a disordered breathingdetection device comprising a sensor system configured to detect arespiration pattern of one or more respiration cycles. The devicefurther includes a detector system coupled to the sensor system. Thedetector system is configured to determine one or more characteristicsof the respiration pattern and classify the respiration pattern asdisordered breathing using the one or more characteristics of therespiration pattern. At least one of the sensor system and the detectorsystem uses an implantable component.

In a further embodiment of the invention, a disordered breathingdetection system includes means for detecting a respiration pattern ofone or more respiration cycles, means for determining one or morecharacteristics of the respiration pattern, and means for classifyingthe respiration pattern as disordered breathing based on the one or morecharacteristics of the respiration pattern, wherein at least one of themeans for detecting, means for determining, and means for classifyinguses an implantable component.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of a disordered breathing detector inaccordance with an embodiment of the invention;

FIG. 2 is a partial view of one embodiment of an implantable medicaldevice that may be used for detection of disordered breathing inaccordance with an embodiment of the invention;

FIG. 3 is a system block diagram of an implantable medical device withwhich disordered breathing detection may be implemented in accordancewith an embodiment of the invention;

FIG. 4 is a graph of transthoracic impedance used in connection withdisordered breathing detection according to an embodiment of theinvention;

FIGS. 5A-B are flow graphs illustrating methods of detecting disorderedbreathing according to an embodiment of the invention;

FIG. 6 is a flow graph illustrating a method of sleep detection used inconjunction with detection of disordered breathing according to anembodiment of the invention;

FIG. 7A is a graph of an accelerometer signal indicating patientactivity over time that may be used to implement a disordered breathingdetection method in accordance with an embodiment of the presentinvention;

FIG. 7B is a graph of a heart rate signal indicating patient activityover time that may be used to implement a disordered breathing detectionmethod in accordance with an embodiment of the present invention;

FIG. 8 is a graph of a minute ventilation signal indicating patientrespiration that may be used to implement a disordered breathingdetection method in accordance with an embodiment of the presentinvention;

FIG. 9 is a graph illustrating adjustment of an accelerometer sleepthreshold using an MV signal in accordance with an embodiment of theinvention;

FIG. 10 is a flow graph of a method of detecting disordered breathingaccording to a method of the invention;

FIGS. 11A-B are graphs of partial respiration patterns illustratingrespiration cycle intervals in accordance with a method of theinvention;

FIGS. 12A-B are graphs illustrating normal and disordered respirationpatterns;

FIG. 13 is a flow graph of a method of detecting disordered breathingaccording to a method of the invention;

FIG. 14 is a graph of a respiration signal illustrating a breathinginterval and a duration threshold in accordance with an embodiment ofthe invention;

FIG. 15 is a graph of a respiration signal illustrating a durationthreshold and a tidal volume threshold in accordance with an embodimentof the invention;

FIGS. 16A-E illustrate respiration patterns that may be classified asdisordered breathing episodes in accordance with an embodiment of theinvention; and

FIG. 17 is a flow graph of a method of detecting disordered breathing inaccordance with an embodiment of the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings which form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

An adequate duration and quality of sleep is required to maintainphysiological homeostasis. Prolonged sleep deprivation or periods ofpoor quality sleep ultimately will have serious health consequences.Disordered breathing, such as sleep apnea and hypopnea, is a major causeof interrupted sleep. People suffering from sleep apnea repeatedly stopbreathing during sleep. Hypopnea is a related condition, characterizedby periods of abnormally slow or shallow breathing.

Sleep apnea/hypopnea may be obstructive, central, or a mixture of thetwo types. Obstructive sleep apnea/hypopnea is the most common type andis typically caused by a blockage of the airway, usually when the softtissue in the throat collapses and closes during sleep. In central sleepapnea/hypopnea, the airway is not blocked but there is an interruptionin signals from the brain controlling breathing. With eachapnea/hypopnea event, the person may briefly arouse in order to resumebreathing. The frequent interruptions during sleep result in extremelyfragmented sleep of poor quality. Untreated, sleep apnea/hypopnea has anumber of adverse health and quality of life consequences ranging fromhigh blood pressure and other cardiovascular diseases to memoryproblems, headaches and degradation of social and work relatedactivities.

Diagnosis of the conditions causing sleep disturbances, includingdisordered breathing, may require people suffering from sleep disordersto spend one or more nights in a sleep laboratory. In the sleeplaboratory setting, a patient can be instrumented for data acquisitionand observed by trained personnel. Polysomnography may be used todiagnose and determine the severity of sleep apnea/hypopnea. During thisprocedure, a variety of physiological functions are externally detectedand recorded during sleep, such as the electrical activity in the brain,eye movement, muscle activity, heart rate, respiratory effort, and bloodoxygen levels. Manual evaluation of these physiological functions isperformed by a technician and used to diagnose disordered breathing suchas sleep apnea/hypopnea and assess possible therapeutic interventions.

Testing in a sleep laboratory setting presents a number of obstacles inacquiring an accurate picture of a patient's typical sleep patterns. Forexample, spending a night in a laboratory typically causes a patient toexperience a condition known as “first night syndrome,” involvingdisrupted sleep during the first few nights in an unfamiliar location.Furthermore, sleeping while instrumented and observed may not result ina realistic perspective of the patient's normal sleep patterns.

Accurate detection of the type, onset, termination, frequency, duration,and severity of disordered breathing may be helpful in tailoringappropriate therapy for patients suffering from sleep disorders. Sleepapnea/hypopnea may be treated in a number of ways, including electricalstimulation therapy including cardiac rhythm management therapy (CRM)and/or hypoglossal nerve stimulation, for example. Respiratory therapyfor sleep apnea/hypopnea may include techniques such as continuouspositive airway pressure (CPAP). Mechanical therapy, ranging from dentalappliances that reposition the lower jaw to surgical techniques such asuvulopalatopharyngoplasty (UPPP), a procedure to remove excess tissue atthe back of the throat, may also be used. Each of these methods, as wellas other methods for treating breathing disorders, may be improved byreliable detection of the type and severity of sleep apnea or hypopnea.

Various embodiments of the invention involve detecting disorderedbreathing based on one or more sensed signals. One embodiment of theinvention involves determining that the patient is asleep, sensingsignals indicative of disordered breathing, and detecting disorderedbreathing based on the sensed signals. Methods of sleep detection aredescribed in commonly owned U.S. Pat. No. 7,189,204, which is herebyincorporated herein by reference.

According to certain embodiments of the invention, at least one of thesteps of determining sleep, sensing the signals associated withdisordered breathing, and detecting disordered breathing is implementedusing an implantable device. For example, the signals associated withdisordered breathing may be sensed using implantable sensors andanalyzed by an external disordered breathing detector. In oneconfiguration, some or all of the sensors may have remote communicationcapabilities, such as a wireless Bluetooth communications link. Thewireless communications link couples the internal sensor or sensors tothe external disordered breathing detector. The sensed signals aretransmitted from the internal sensors to the external disorderedbreathing detector over the wireless communications link.

In another example, the disordered breathing detector is an implantabledevice and one or all of the sensors are located externally on or nearthe patient. The sensed signals are transmitted from the externalsensors to the implanted disordered breathing detector over a wirelesscommunication link.

Another embodiment of the invention involves detection of a respirationpattern of one or more respiration cycles and determining thecharacteristics of the respiration pattern. A respiration pattern isclassified as disordered breathing based on the characteristics of therespiration patterns. At least one of detecting the respiration pattern,determining the characteristics of the respiration pattern, andclassifying the respiration patterns is performed at least in partimplantably.

In one configuration, the disordered breathing detector is a componentof a device that also performs other functions, such as cardiacpacemaker or defibrillation functions. One or all of the sensors may bewirelessly coupled to the implantable device, for example. Respirationpatterns may be classified by determining inspiration, expiration, andnon-breathing intervals. Characteristics of the respiration patternsinclude respiration rate, respiration tidal volume, and duration ofrespiration cycle intervals and/or duration of the respiration pattern.Each characteristic of a respiration pattern may be expressed as amedian, moving average, or weighted average, for example.

Indices associated with disordered breathing conditions are established.The indices may represent values or characteristics of the sensedsignals associated with disordered breathing that indicate disorderedbreathing is occurring. The indices may be established using clinicaldata acquired from a similarly situated group of patients, or from thepatient for whom disordered breathing is to be detected. Furthermore,the apnea or hypopnea indices established for a particular patient maytake into account the presence of patient conditions such ascardiopulmonary diseases, e.g., heart failure and/or chronic obstructivepulmonary disease.

Disordered breathing may be detected by comparing one or more disorderedbreathing indices to the sensed signals associated with disorderedbreathing. In one example, disordered breathing is determined bycomparing disordered breathing indices to characteristics of respirationpatterns classified in accordance with the principles of the invention.

Another embodiment of the invention involves detecting disorderedbreathing episodes based on one or more breaths of excessive duration orinsufficient volume. According to this embodiment, an apnea episode isdetected if a breath interval exceeds a duration threshold. A hypopneaepisode is detected if the tidal volume of successive breaths remainsless than the tidal volume threshold for a period in excess of theduration threshold. Mixed apnea/hypopnea episodes may also occur,wherein the period of disordered breathing is characterized by shallowbreaths and non-breathing intervals. During the mixed apnea/hypopneaepisodes, the tidal volume of each breath remains less than the tidalvolume threshold and one or more breath intervals exceeds a periodexceeding the duration threshold.

According to an embodiment of the present invention, methods ofdisordered breathing detection are implemented in an implantable cardiacrhythm management (CRM) system configured as a dual chamber pacemakerdevice that may operate in numerous pacing modes known in the art.Systems and methods of the present invention may also be implemented invarious types of implantable or external diagnostic medical devicesincluding, for example, polysomnography devices, respiratory monitors,and cardiac monitors. In addition, methods of the present invention maybe implemented in a number of implantable or external therapeuticmedical devices such as continuous positive airway pressure (CPAP)devices or hypoglossal nerve stimulators.

FIG. 1 is a block diagram of a disordered breathing detection device 100that may be used to detect disordered breathing in accordance withvarious embodiments of the invention. The disordered breathing detectiondevice 100 includes a number of sensors 101, 102, 103, 104 that sensesignals associated with sleep and/or disordered breathing. These signalsmay be processed to produce signal parameters associated with sleepand/or disordered breathing. For example, an electrical cardiac signalmay be sensed and cardiac signal parameters including heart rate and QTinterval may be determined from the electrical cardiac signal. In thecontext of the present invention, either a sensed signal or a derivedsignal parameter is generally referred to herein with the term signal.

A representative set of signals associated with sleep and/or disorderedbreathing include body movement, heart rate, QT interval, eye movement,respiration rate, transthoracic impedance, tidal volume, minuteventilation, body posture, electroencephalogram (EEG), electrocardiogram(ECG), electrooculogram (EOG), electromyogram (EMG), muscle tone, bodytemperature, pulse oximetry, blood pressure, time of day, and historicalsleep times.

According to various embodiments, a set of sleep-related signals may beused for sleep detection and a separate or overlapping set of signalsassociated with disordered breathing may be used for disorderedbreathing detection. Sleep detection involves comparing a sleepdetection signal derived from a sleep detection sensor 101 to a sleepthreshold or index to detect the onset and termination of sleep. Thesleep threshold may be a particular value of the sleep detection signalor another feature of the signal. A second sleep-related signal derivedfrom a threshold adjustment sensor 102 may be used to adjust the sleepthreshold or index. Although one sleep detection sensor and onethreshold adjustment sensor are shown in FIG. 1, any number of sleepthresholds corresponding to any number of sleep detection sensors may beused. Furthermore, signals from any number of threshold adjustmentsensors may be used to adjust the values or features of the sleepthresholds associated with a plurality of sleep detection signals.Additional sleep-related signals derived from one or more sleepconfirmation sensors 103 may be used to confirm the onset and/ortermination of the sleep condition.

In addition to the sleep detection sensors discussed above, one or moredisordered breathing sensors 104 may be used to detect episodes ofdisordered breathing such as sleep apnea or hypopnea, for example. Insome cases the signals derived from the sleep detection 101, thresholdadjustment 102, and/or confirmation sensors 103 may also be used fordisordered breathing detection. In other cases, one or more disorderedbreathing sensors 104 may sense a different set of signals than thesleep-related signals.

The outputs of sensors 101, 102, 103, 104 are received by a sensordriver/detector system 110 having detection circuitry 121, 122, 123,124, that may include, for example, amplifiers, signal processingcircuitry, timing, and/or A/D conversion circuitry for each sensoroutput. The driver/detector system 110 may further include sensor drivecircuitry 111, 112, 113, 114 as required to activate the sensors 101,102, 103, 104.

A disordered breathing detector 130, according to one embodiment,transmits control signals to the drive circuitry 111, 112, 113, 114 andreceives signals from the detection circuitry 121, 122, 123, 124. Thedisordered breathing detector 130 may include a sleep detector 134 fordetermining the onset and termination of a sleep state. The disorderedbreathing detector 130 may also include a microprocessor controller 131that cooperates with the sleep detector 134 and the memory circuitry 132for implementing disordered breathing detection methods of the presentinvention. The memory circuitry 132 may be used to store program codeand/or data to implement disordered breathing detection and to storethresholds or indices associated with sleep detection and disorderedbreathing detection, such as, sleep thresholds, and sleep apnea orhypopnea detection indices. The memory circuitry 132 may also be used tostore historical data regarding disordered breathing episodes.

In one embodiment of disordered breathing detection, a sleep detector134 is used to determine that the patient is asleep. The sleep detector134 may be configured to compare the value of a first sleep-relatedsignal, derived from a sleep detection sensor 101, to a sleep thresholdadjusted by a second sleep-related signal, derived from a thresholdadjustment sensor 102. Onset or termination of sleep may be determinedin the sleep detector 134 based on the comparison of the value of thefirst sleep-related signal to the sleep threshold. The sleep detector134 may use one or more sleep thresholds associated with one or moresleep-related signals derived from a number of sensors. Further, thesleep detector 134 may use one or more sleep-related signals to adjustthe sleep thresholds. In addition, the sleep detector 134 may confirmthe onset or termination of sleep using an additional number ofsleep-related signals.

According to various embodiments, the disordered breathing detector 130includes one or more sensors for sensing signals associated withdisturbed breathing. The signals associated with disordered breathingmay include signals associated with cardiac activity, such as electricalactivity of the heart, and/or signals associated with respiration,including transthoracic impedance. The signals associated with cardiacactivity may be used to derive parameters such as heart rate and QTinterval. The signals associated with respiration, e.g., transthoracicimpedance, may be used to derive parameters including respiration rate,tidal volume, and minute ventilation.

One method of disordered breathing detection involves sensing one ormore respiration signals to detect a respiration pattern. For example,transthoracic impedance may be sensed and used to acquire patterns ofrespiration. Disordered breathing, such as sleep apnea and hypopnea, maybe detected based on characteristics of the respiration patterns,including characteristics such as tidal volume, respiration rate,duration of the respiration pattern, and duration of one or morerespiration intervals within the respiration pattern.

The disordered breathing detector 130 may include output circuitry 133for communicating output signals associated with the detection andanalysis of disordered breathing to other diagnostic or therapeuticdevices, other components of the disordered breathing detection device,a data storage device or a display device. The output signals mayinclude, for example, a sleep apnea or hypopnea detection signalindicating that sleep apnea/hypopnea has been detected, as well as datarelated to the disturbed breathing episodes, including data providingthe severity and duration of one or more disordered breathing episodes.The disordered breathing detector may communicate with another deviceover a wired or wireless communication channel, for example.

The sensors 101, 102, 103, 104 may comprise implantable sensors and/orexternal sensors. In one embodiment, the sensors 101, 102, 103, 104 arecoupled to the driver/detector circuitry 110 and thus to the detector130 through a wired connection. In another embodiment, one or more ofthe sensors 101, 102, 103, 104 and the associated driver/detectorcircuitry 110 are incorporated into sensing devices that includewireless communication capabilities, e.g., a Bluetooth transmitter ortransceiver, and may be coupled to the detector 130 through a wirelesslink. The detector 130 and driver/detector circuitry 110 may beincorporated into an implantable or external device.

FIG. 2 is a partial view of one embodiment of an implantable medicaldevice that may be used in connection with disordered breathingdetection in accordance with the principles of the invention. Theimplantable device illustrated in FIG. 2 is a cardiac rhythm management(CRM) system that includes an implantable pacemaker 200 electrically andphysically coupled to an intracardiac lead system 202. The intracardiaclead system 202 is implanted in a human body with portions of theintracardiac lead system 202 inserted into a heart 201. The intracardiaclead system 202 is used to detect and analyze electric signals producedby the heart 201 and to provide electrical energy to the heart 201 underpredetermined conditions to treat cardiac arrhythmias of the heart 201.

The CRM 200 depicted in FIG. 2 is a dual chamber device, capable ofsensing signals from the right atrium and right ventricle and providingpacing pulses to the right atrium and the right ventricle. Low energypacing pulses may be delivered to the heart to regulate the heart beator maintain a lower rate heart beat, for example. In a configurationthat includes cardioversion/defibrillation capabilities, high energypulses may also be delivered to the heart if an arrhythmia is detectedthat requires cardioversion or defibrillation.

The intracardiac lead system 202 includes a right ventricular leadsystem 204 and a right atrial lead system 205. The right ventricularlead system 204 includes an RV-tip pace/sense electrode 212 and one ormore impedance electrodes 213, 214, 216 suitable for measuringtransthoracic impedance. In one configuration, impedance sense and driveelectrodes 216, 214, 213 may be configured as ring electrodes.

The right ventricular lead system 204 depicted in FIG. 2 includes animpedance drive electrode 213 located in the right ventricle 218. Theright ventricular lead system 204 also includes an impedance senseelectrode 214 that may be located in the right atrium 220. Alternativelyor additionally, an impedance sense electrode 216 may be located in thesuperior right atrium 220 or near the right atrium 220 within thesuperior vena cava 222.

A two-electrode impedance sensing configuration is also possible,wherein the right ventricular lead system includes an impedance driveelectrode 213 and a tip electrode 212. In this configuration, the tipelectrode 212 is used as the impedance sense electrode. Other locationsand combinations of impedance sense and drive electrodes are alsopossible.

In the configuration of FIG. 2, the intracardiac lead system 202 ispositioned within the heart 201, with portions of the atrial lead system205 extending into the right atrium 220 and portions of the rightventricular lead system 204 extending through the right atrium 220 intothe right ventricle 218. The A-tip electrode 256 is positioned at anappropriate location within the right atrium 220 for pacing the rightatrium 220 and sensing cardiac activity in the right atrium 220. TheRV-tip electrode 212 is positioned at an appropriate location within theright ventricle 218 for pacing the right ventricle 218 and sensingcardiac activity in the right ventricle 218.

Additional configurations of sensing, pacing, and defibrillationelectrodes can be included in the intracardiac lead system to allow forvarious sensing, pacing, and defibrillation capabilities of multipleheart chambers. In one configuration, the right ventricular and rightatrial leads may include additional electrodes for bipolar sensingand/or pacing, for example. Further, the right ventricular and rightatrial leads may also include additional electrodes for cardioversion ordefibrillation.

In other configurations, the intracardiac lead system may have only asingle lead with electrodes positioned in the right atrium or the rightventricle to implement disordered breathing detection and single chambercardiac pacing and sensing. In yet other embodiments, the lead systemmay include intravenous leads that are advanced into the coronary sinusand coronary veins to locate the distal electrode(s) adjacent to theleft ventricle or the left atrium. Other lead and electrode arrangementsand configurations known in the art are also possible and considered tobe within the scope of the present system.

Referring now to FIG. 3, there is shown a block diagram of an embodimentof a CRM system 300 configured as a pacemaker and suitable forimplementing a disordered breathing detection methodology of the presentinvention. FIG. 3 shows the CRM 300 divided into functional blocks. Itwill be understood by those skilled in the art that there exist manypossible configurations in which these functional blocks can be arrangedand implemented. The example depicted in FIG. 3 is one possiblefunctional arrangement. The CRM 300 includes disordered breathingdetection circuitry 320 for receiving signals associated with sleepand/or disordered breathing and detecting disordered breathing inaccordance with principles of the invention.

In one embodiment, disordered breathing detection circuitry 320 isincorporated as part of the CRM circuitry 310 encased and hermeticallysealed in a housing 390 suitable for implanting in a human body. Powerto the CRM 300 is supplied by an electrochemical battery power supply312 housed within the CRM 300. A connector block (not shown) isadditionally attached to the CRM housing 390 to allow for the physicaland electrical attachment of the intracardiac lead system conductors tothe CRM circuitry 310.

The CRM circuitry 310 may be configured as a programmablemicroprocessor-based system, with circuitry for detecting disorderedbreathing in addition to providing pacing therapy to the heart. Cardiacsignals may be detected by the detector circuitry 360 and delivered to apacemaker control system 350. Pace pulses controlled by the pacemakercontrol 350 and generated by the pulse generator 340 may be delivered tothe heart to treat various arrhythmias of the heart.

The memory circuit 316 may store parameters for various deviceoperations involving disordered breathing detection and/or cardiacpacing and sensing. The memory circuit 316 may also store dataassociated with physiological or other signals received by components ofthe CRM circuitry 310, such as the impedance drive/sense circuitry 330,the cardiac signal detector system 360, the accelerometer 335, and othercircuitry 336, 337 associated with external and/or implantable sensors.

The disordered breathing detection circuitry 320 receives signalsderived from the cardiac signal detector system 360, the impedancedriver/detector circuitry 330, and the accelerometer 335. The disorderedbreathing detector 320 may optionally receive signals associated withdisordered breathing from additional sensor driver/detector circuitry336 coupled to one or more additional implantable sensors 217 through alead system. The disordered breathing detector 320 may optionallyreceive signals associated with disordered breathing from sensorreceiver circuitry 337 coupled to one or more implantable or externalsensors 215 through a wireless communication link. Detection ofdisordered breathing may include detection of sleep onset andtermination implemented in sleep detection circuitry 321 according tothe principles of the present invention.

Historical data storage 318 may be coupled to the disordered breathingdetection circuitry 320 for storing historical data related todisordered breathing. Such data may be transmitted to an externalprogrammer unit 380 and used for various diagnostic or other purposesand as needed or desired.

Telemetry circuitry 314 is coupled to the CRM circuitry 310 to allow theCRM 300 to communicate with an external programmer unit 380. In oneembodiment, the telemetry circuitry 314 and the programmer unit 380 usea wire loop antenna and a radio frequency telemetric link to receive andtransmit signals and data between the programmer unit 380 and telemetrycircuitry 314. In this manner, programming commands and data may betransferred between the CRM circuitry 310 and the programmer unit 380during and after implant. The programming commands allow a physician toset or modify various parameters used by the CRM. These parameters mayinclude thresholds or indices for use during disordered breathingdetection, such as sleep thresholds, disordered breathing indices andparameters, and apnea and hypopnea indices. In addition, the CRM system300 may download to the programmer unit 380 stored data pertaining todisordered breathing episodes, including the duration, severity, episoderespiratory signals, and frequency of the episodes, for example.

Signals associated with patient activity may be detected through the useof an accelerometer 335 that may be positioned within the housing 390 ofthe CRM 300. The accelerometer responds to patient activity and theaccelerometer signal may be correlated with activity level, workload,and/or posture. Signals derived from the accelerometer 335 are coupledto the disordered breathing detection circuitry 320 and may also be usedby the pacemaker circuitry 350 for implementing a rate adaptive pacingregimen, for example.

The impedance sense electrode 214, the impedance drive electrode 213,and the impedance driver/detector circuitry 330 are used to measuretransthoracic impedance. The transthoracic impedance measurement may beused to calculate various parameters associated with respiration. Underthe control of the disordered breathing detection circuitry 320, theimpedance driver circuitry 332 produces a current that flows through theblood between the impedance drive electrode 213 and the can electrode309. The voltage at the impedance sense electrode 214 relative to thecan electrode 309 changes as the transthoracic impedance changes. Thevoltage signal developed between the impedance sense electrode 214 andthe can electrode 309 is detected by the impedance sense amplifier 334located within the impedance driver/detector circuitry 330. This signalmay be further filtered, digitized, or otherwise processed within theimpedance driver/detector circuitry 330 and delivered to the disorderedbreathing detection circuitry 320.

The voltage signal developed at the impedance sense electrode 214,illustrated in FIG. 4, is proportional to the transthoracic impedance,with the impedance increasing during respiratory inspiration anddecreasing during respiratory expiration. The peak-to-peak transition ofthe impedance measurement is proportional to the amount of air inhaledin one breath, denoted the tidal volume, also illustrated in FIG. 4. Theimpedance measurement may be further processed to determine the minuteventilation corresponding to the volume of air moved per minute.

Cardiac parameters, including heart rate, heart rate regularity, and QTinterval, for example, may also be used in connection with the detectionof disordered breathing. Turning back to FIG. 3, cardiac signals aresensed through use of the RV-tip and RA-tip sense electrodes 212, 256.More particularly, the right ventricle signal may be detected as avoltage developed between the RV-tip electrode 212 and the can electrode309. Right ventricle cardiac signals are sensed and amplified by a rightventricle V-sense amplifier 362 located in the detector system 360. Theoutput of the right ventricle V-sense amplifier 362 may be coupled, forexample, to a signal processor and A/D converter within the detectorsystem 360. The processed right ventricle signals may be delivered tothe pacemaker control 350 and the disordered breathing detectioncircuitry 320.

Right atrium cardiac signals are sensed and amplified by a right atrialA-sense amplifier 364 located in the detector system 360. The output ofthe right atrium A-sense amplifier 364 may be processed by signalprocessing circuitry and received by the pacemaker control 350 and thedisordered breathing detection circuitry 320.

The pacemaker control 350 communicates pacing control signals to thepulse generator circuitry 340 for delivering pacing stimulation pulsesto the RV-tip and RA-tip electrodes 212 and 256, respectively, accordingto a pre-established pacing regimen under appropriate conditions.

In addition to the cardiac, respiration, and activity signals discussedabove, additional or alternative signals useful in detection ofdisordered breathing may be sensed using external and/or implantedsensors 215, 217 and coupled to the disordered breathing detectioncircuitry 320 through sensor driver/detector and/or sensor receivercircuitry 336, 337. The additional or alternative signals may be used toimplement or confirm disordered breathing detection according to theprinciples of the invention.

FIG. 5A is a flowchart illustrating a method of detecting disorderedbreathing in a patient according to an embodiment of the invention.According to this method, disordered breathing may be detected by firstdetermining that the patient has fallen asleep 510. One method ofdetermining sleep involves establishing a sleep threshold associatedwith a first sleep-related signal. For example, the sleep threshold maybe established from analysis of clinical data indicating a sleepthreshold using a group of subjects. Alternatively or additionally, thesleep threshold may be established using historical data taken from theparticular patient for whom the sleep condition is to be determined.

Sleep may be determined based on a comparison of the first sleep-relatedsignal to the established threshold. For example, if the firstsleep-related signal falls below the sleep threshold, sleep onset isdetermined. If the first sleep-related signal rises above the sleepthreshold, sleep termination is determined. As will be understood, sleeponset or termination may be determined based on a signal rising abovethe sleep threshold or falling below the sleep threshold depending onthe nature of the first sleep-related signal and the sleep threshold.

One or more additional sleep-related signals may be used to adjust thesleep threshold. For example, if a sleep-related signal used to adjustthe sleep threshold indicates a state incompatible with sleep, forexample, a high activity level, the sleep threshold may be adjusteddownward to require sensing a decreased level of the first sleep-relatedsignal before a sleep condition is detected.

Alternatively or additionally, sleep may be established based on time ofday. Because most patients' sleep patterns are reasonably consistent,establishing sleep based on time of day may be an acceptable techniquein some circumstances. Also, an acceptable measurement of the level ofsleep-disordered breathing experienced by a patient can be determinedusing a portion of the patient's sleep period. Thus, only times of daywhen the patient is likely to be sleeping, e.g., 12 am to 4 am, may needto be used to detect episodes of disordered breathing.

Signals associated with disordered breathing are sensed 520 while thepatient is asleep. For example, various cardiac signals and derivedparameters, such as heart rate and QT interval, may indicate disorderedbreathing. Furthermore, respiratory signals and parameters derived fromthe signals, such as respiratory cycle, minute ventilation, and tidalvolume, may indicate disordered breathing. The signals and/or derivedparameters associated with disordered breathing may be used to detectsleep disordered breathing 530 according to the principles of theinvention.

As previously discussed, the signals associated with sleep and/ordisordered breathing may be sensed using sensors that are implanted inthe patient, attached externally to the patient, or located in proximityof the patient, for example. The signals may include any signalassociated with the condition of sleep or disordered breathing, such asany or all of the representative set of signals and parameters listedabove.

FIG. 5B illustrates a more detailed flow chart of a method for detectingsleep apnea or hypopnea according to the principles of the invention.Prior to detection of disordered breathing episodes, a sleep threshold540 and disordered breathing indices 545 are established. The sleepthreshold and disordered breathing indices may be associated withsignals or derived parameters indicative of sleep and/or disorderedbreathing as listed above. For example, the sleep threshold may berelated to patient activity as indicated by the patient's heart rate orthe patient's motion sensed by an accelerometer located in or on thepatient. Disordered breathing indices may be established using signalsassociated with disordered breathing and parameters derived from thesignals associated with disordered breathing including heart rate,respiration rate, and/or tidal volume, for example. Disordered breathingindices may be used to detect a sleep apnea or hypopnea condition. Itwill be understood that in some circumstances sleep determination anddisordered breathing detection may be implemented using the same signalsand/or parameters or different set of signals and/or parameters.

Sleep-related signals, including a first sleep-related signal used todetermine the sleep condition, and one or more threshold adjustmentsleep-related signals, are sensed 550. The sleep threshold previouslyestablished may be adjusted using the one or more threshold adjustmentsignals 555. So long as the first sleep-related signal exceeds the sleepthreshold 560, the patient is determined to be awake 570, and the firstsleep-related signal and the threshold adjustment signals continue to bemonitored 550. If the first sleep-related signal falls below the sleepthreshold 560, an onset of the sleep condition is detected 565.

One or more signals associated with disordered breathing are sensed 575while the patient is asleep. As previously discussed, these signals maycorrespond, for example, to cardiac or respiratory parameters such asheart rate, respiration rate, tidal volume, and minute ventilation. Thesignals associated with disordered breathing are compared 580 topreviously established indices corresponding to sleep apnea. If thesignals are consistent with sleep apnea, then a sleep apnea condition isdetected 585. One or more of the apnea and/or hypopnea indices may beadjusted 587, 597 based on the detected apnea episode.

The signals indicative of disordered breathing are compared 590 topreviously established indices corresponding to hypopnea 590. If thesignals are consistent with hypopnea, then a hypopnea condition isdetected 595. One or more of the apnea and/or hypopnea indices may beadjusted 587, 597 based on the detected hypopnea episode.

The sensitivity of one or more of the apnea or hypopnea indices may beadapted 587, 597 based on characteristics of one or more of thedisordered breathing episodes including, for example, the type,duration, severity, and/or frequency of previously detected disorderedbreathing episodes. For example, detection of a predetermined number ofdisordered breathing episodes within a selected time period may indicatethat additional disordered breathing episodes are likely. Therefore, oneor more of the disordered breathing indices may be modified to morequickly detect the next episode of disordered breathing. The sensitivityof these indices may also be adapted based on the patient'scardiopulmonary condition.

FIG. 6 is a flowchart illustrating a method of sleep detection inaccordance with an embodiment of the invention. For the purposes ofsleep detection described in relation to FIG. 6, signals using anaccelerometer and a minute ventilation sensor are used as thesleep-related signals used for sleep-determination. According to thisembodiment, a preliminary sleep threshold is determined 610 for theaccelerometer signal. For example, the preliminary sleep threshold maybe determined from clinical data taken from a group of subjects orhistorical data taken from the patient over a period of time.

The activity level of the patient is monitored using an accelerometer620 that may be incorporated into an implantable cardiac pacemaker asdescribed above. Alternatively, the accelerometer may be attachedexternally to the patient. The patient's minute ventilation (MV) signalis monitored 625. The MV signal may be derived, for example, using thetransthoracic impedance measurement acquired as described above.Transthoracic impedance may be sensed by implantable sensors and the MVsignal calculated by an implantable cardiac device. Other methods ofdetermining the MV signal are also possible and are considered to bewithin the scope of this invention.

In this example, the accelerometer signal represents the firstsleep-related signal and is compared with the sleep threshold to detectsleep. The MV signal is the threshold adjustment signal used to adjustthe sleep threshold. Additional sleep-related signals, such as heartrate and/or posture may be monitored 630 to confirm sleep.

Threshold adjustment may be accomplished by using the patient's MVsignal to moderate the sleep threshold of the accelerometer signal. Ifthe patient's MV signal is low relative to an expected MV levelassociated with sleep, the accelerometer-based sleep threshold isincreased. Similarly, if the patient's MV signal level is high relativeto an expected MV level associated with sleep, the accelerometer-basedsleep threshold is decreased. Thus, when the patient's MV level is high,a decreased level of activity is required to make the determination thatthe patient is sleeping. Conversely when the patient's MV level isrelatively low, a higher level is required for the sleep determination.The use of at least two sleep-related signals to determine a sleepcondition enhances the accuracy of sleep detection over previous methodsusing only one physiological signal to determine that a patient issleeping.

Various signal processing techniques may be employed to process the rawsensor signals. For example, a moving average of a plurality of samplesof each signal may be calculated and used as the signal. Furthermore,the signals associated with disordered breathing may be filtered and/ordigitized. If the MV signal is high 635 relative to an expected MV levelassociated with sleep, the accelerometer sleep threshold is decreased640. If the MV signal is low 635 relative to an expected MV levelassociated with sleep, the accelerometer sleep threshold is increased645.

If the accelerometer signal is less than or equal to the adjusted sleepthreshold 650 and if the patient is not currently in a sleep state 665,then the patient's heart rate is checked 680 to confirm the sleepcondition. If the patient's heart rate is compatible with sleep 680,then sleep onset 690 is determined. If the patient's heart rate isincompatible 680 with sleep, then the patient's sleep-related signalscontinue to be monitored.

If the accelerometer signal is less than or equal to the adjusted sleepthreshold 650 and if the patient is currently in a sleep state 665, thena continuing sleep state is determined 675 and the patient's signalsassociated with disordered breathing continue to be monitored for sleeptermination to occur. Additional signals, such as heart rate or bodyposture, for example, may optionally be monitored to determine thecontinuation of the sleep state.

If the accelerometer signal is greater than the adjusted sleep threshold650 and the patient is not 660 currently in a sleep state, then thepatient's sleep-related signals continue to be monitored until sleeponset is detected 690. If the accelerometer signal is greater than theadjusted sleep threshold 650 and the patient is 660 currently in a sleepstate, then sleep termination is detected 670.

The graphs of FIGS. 7-9 illustrate the adjustment of theaccelerometer-based sleep threshold using the MV signal. Therelationship between patient activity and the accelerometer and MVsignals is trended over a period of time to determine relative signallevels associated with a sleep condition. FIG. 7A illustrates activityas indicated by the accelerometer signal. The patient's heart rate forthe same period is graphed in FIG. 7B. The accelerometer signalindicates a period of sleep associated with a relatively low level ofactivity beginning at slightly before 23:00 and continuing through 6:00.Heart rate appropriately tracks the activity level indicated by theaccelerometer indicating a similar period of low heart ratecorresponding to sleep. The accelerometer trending is used to establisha preliminary threshold for sleep detection.

FIG. 8 is a graph of baseline trending for an MV signal. Historical dataof minute ventilation of a patient is graphed over an 8 month period.The MV signal trending data is used to determine the MV signal levelassociated with sleep. In this example, a composite MV signal using thehistorical data indicates a roughly sinusoidal shape with the relativelylow MV levels occurring approximately during period from hours 21:00through 8:00. The low MV levels are associated with periods of sleep.

FIG. 9 illustrates adjustment of the accelerometer-based sleep threshold910 using the MV signal. FIG. 9 illustrates the accelerometer-basedsleep threshold 910 superimposed on the accelerometer signal. Aspreviously discussed, if the patient's MV signal is low relative to anexpected MV level associated with sleep, the accelerometer-based sleepthreshold 910 is increased 920. If the patient's MV signal level is highrelative to an expected MV level associated with sleep, theaccelerometer-based sleep threshold is decreased 930. Thus, when thepatient's MV level is high, less activity detected by the accelerometeris required to make the determination that the patient is sleeping. Ifthe patient's MV level is relatively low, a higher activity level mayresult in detection of sleep.

Additional sleep-related signals may be sensed and used to improve thesleep detection mechanism described above. For example, a posture sensormay be incorporated into a pacemaker case and used to detect the postureof the patient. If the posture sensor indicates a vertical posture, thenthe posture indicator may be used to override a determination of sleepusing the accelerometer and MV signals. Other signals may also be usedin connection with the confirmation of sleep detection.

A method of detecting disordered breathing according to anotherembodiment of the invention is illustrated in the flow chart of FIG. 10.According to this method, signals associated with respiration are sensedand used to detect 1010 a respiration pattern. Characteristics of therespiration pattern are determined 1020. The respiration pattern isclassified 1030 as sleep disordered breathing based on thecharacteristics of the respiration pattern. At least one of detectingthe respiration pattern, determining the characteristics of therespiration pattern, and detecting disordered breathing based oncharacteristics of the respiration pattern is performed at least in partimplantably.

In one configuration, determining the characteristics of the respirationpattern includes determining intervals of the patient's respirationcycles. FIGS. 11A and 11B illustrate portions of a respiration patterndetected using transthoracic impedance measurements acquired asdescribed in more detail above.

FIG. 11A illustrates respiration intervals used for sleep apneadetection according to an embodiment of the invention. A respirationcycle is divided into an inspiration period corresponding to the patientinhaling, an expiration period, corresponding to the patient exhaling,and a non-breathing period occurring between inhaling and exhaling.Respiration intervals are established using inspiration 1110 andexpiration 1120 thresholds. The inspiration threshold 1110 marks thebeginning of an inspiration period 1130 and is determined by thetransthoracic impedance signal rising above the inspiration threshold1110. The inspiration period 1130 ends when the transthoracic impedancesignal is maximum 1140. A maximum transthoracic impedance signal 1140corresponds to both the end of the inspiration interval 1130 and thebeginning of the expiration interval 1150. The expiration interval 1150continues until the transthoracic impedance falls below an expirationthreshold 1120. A non-breathing interval 1160 starts from the end of theexpiration period 1150 and continues until the beginning of the nextinspiration period 1170.

Detection of sleep apnea and severe sleep apnea according to theprinciples of the invention are illustrated in FIG. 11B. The patient'srespiration signals are monitored and the respiration cycles are definedaccording to inspiration 1130, expiration 1150, and non-breathing 1160intervals as described in connection with FIG. 11A. A condition of sleepapnea is detected when a non-breathing period 1160 exceeds a firstpredetermined interval 1190, denoted the sleep apnea interval. Acondition of severe sleep apnea is detected when the non-breathingperiod 1160 exceeds a second predetermined interval 1195, denoted thesevere sleep apnea interval. For example, sleep apnea may be detectedwhen the non-breathing interval exceeds about 10 seconds, and severesleep apnea may be detected when the non-breathing interval exceedsabout 20 seconds.

Hypopnea is a condition of disordered breathing characterized byabnormally shallow breathing. FIGS. 12A-B are graphs of tidal volumederived from transthoracic impedance measurements that compare the tidalvolume of a normal breathing cycle to the tidal volume of a hypopneaepisode. FIG. 12A illustrates normal respiration tidal volume and rate.As shown in FIG. 12B, hypopnea involves a period of very shallowrespiration at an otherwise normal rate.

According to an embodiment of the invention, hypopnea is detected bycomparing a patient's respiratory tidal volume to a hypopnea tidalvolume index. The tidal volume for each respiration cycle is derivedfrom transthoracic impedance measurements acquired in the mannerdescribed above. The hypopnea tidal volume index may be establishedusing clinical results providing a representative tidal volume andduration of hypopnea events. In one configuration, hypopnea is detectedwhen an average of the patient's respiratory tidal volume taken over aselected time interval falls below the hypopnea tidal volume index.Furthermore, various combinations of hypopnea cycles and non-breathingintervals may be used to detect hypopnea, where the non-breathingintervals are determined as described above.

FIG. 13 is a flow chart illustrating a method of apnea and/or hypopneadetection according to principles of the invention. Various parametersare established 1301 before analyzing the patient's respiration fordisordered breathing episodes, including, for example, inspiration andexpiration thresholds, sleep apnea interval, severe sleep apneainterval, and hypopnea tidal volume index.

The patient's transthoracic impedance is measured 1305 as described inmore detail above. If the transthoracic impedance exceeds 1310 theinspiration threshold, the beginning of an inspiration interval isdetected 1315. If the transthoracic impedance remains below 1310 theinspiration threshold, then the impedance signal is checked 1305periodically until inspiration 1315 occurs.

During the inspiration interval, the patient's transthoracic impedanceis monitored until a maximum value of the transthoracic impedance isdetected 1320. Detection of the maximum value signals an end of theinspiration period and a beginning of an expiration period 1335.

The expiration interval is characterized by decreasing transthoracicimpedance. When the transthoracic impedance falls below 1340 theexpiration threshold, a non-breathing interval is detected 1355.

If the transthoracic impedance does not exceed 1360 the inspirationthreshold within a first predetermined interval 1365, denoted the sleepapnea interval, then a condition of sleep apnea is detected 1370. Severesleep apnea is detected 1380 if the non-breathing period extends beyonda second predetermined interval 1375, denoted the severe sleep apneainterval.

When the transthoracic impedance exceeds 1360 the inspiration threshold,the tidal volume from the peak-to-peak transthoracic impedance iscalculated, along with a moving average of past tidal volumes 1385. Thepeak-to-peak transthoracic impedance provides a value proportional tothe tidal volume of the respiration cycle. This value is compared 1390to a hypopnea tidal volume index. If the peak-to-peak transthoracicimpedance is consistent with 1390 the hypopnea tidal volume index, thena hypopnea cycle is detected 1395. If a series of hypopnea cycles aredetected, a hypopnea episode is detected.

Additional sensors, such as motion sensors and/or posture sensors, maybe used to confirm or verify the detection of a sleep apnea or hypopneaepisode. The additional sensors may be employed to prevent false ormissed detections of sleep apnea/hypopnea due to posture and/or motionrelated artifacts.

Another embodiment of the invention involves classifying respirationpatterns as disordered breathing episodes based on the breath intervalsand/or tidal volumes of one or more respiration cycles within therespiration patterns. According to this embodiment, the duration andtidal volumes associated with a respiration pattern are compared toduration and tidal volume thresholds. The respiration pattern isdetected as a disordered breathing episode based on the comparison.

According to principles of the invention, a breath interval 1430 isestablished for each respiration cycle. A breath interval represents theinterval of time between successive breaths, as illustrated in FIG. 14.A breath interval 1430 may be defined in a variety of ways, for example,as the interval of time between successive maxima 1410, 1420 of theimpedance signal waveform.

Detection of disordered breathing, in accordance with methods of theinvention, involves the establishment of a duration threshold and atidal volume threshold. If a breath interval exceeds the durationthreshold, an apnea event is detected. Detection of sleep apnea, inaccordance with this embodiment, is illustrated in the graph of FIG. 14.Apnea represents a period of non-breathing. A breath interval 1430exceeding a duration threshold 1440, comprises an apnea episode.

Hypopnea may be detected using the duration threshold and tidal volumethreshold. A hypopnea event represents a period of shallow breathing.Each respiration cycle in a hypopnea event is characterized by a tidalvolume less than the tidal volume threshold. Further, the hypopnea eventinvolves a period of shallow breathing greater than the durationthreshold.

Hypopnea detection in accordance with an embodiment of the invention isillustrated in FIG. 15. Shallow breathing is detected when the tidalvolume of one or more breaths is below a tidal volume threshold 1510. Ifthe shallow breathing continues for an interval greater than a durationthreshold 1520, then the breathing pattern represented by the sequenceof shallow respiration cycles, is classified as a hypopnea event.

Disordered breathing events may comprise a mixture of apnea and hypopnearespiration cycles. As illustrated in FIGS. 16A-E, a respiration patterndetected as a disordered breathing episode may include only an apnearespiration cycle 1610 (FIG. 16A), only hypopnea respiration cycles 1650(FIG. 16D), or a mixture of hypopnea and apnea respiration cycles 1620(FIG. 16B), 1630 (FIG. 16C), 1660 (FIG. 16E). A disordered breathingevent 1620 may begin with an apnea respiration cycle and end with one ormore hypopnea cycles. In another pattern, the disordered breathing event1630 may begin with hypopnea cycles and end with an apnea cycle. In yetanother pattern, a disordered breathing event 1660 may begin and endwith hypopnea cycles with an apnea cycle in between the hypopnea cycles.

FIG. 17 is a flow chart of a method for detecting disordered breathingby classifying breathing patterns using breath intervals in conjunctionwith tidal volume and duration thresholds as described in connectionwith FIGS. 14-16 above. In this example, a duration threshold and atidal volume threshold are established for determining both apnea andhypopnea breath intervals. An apnea episode is detected if the breathinterval exceeds the duration threshold. A hypopnea episode is detectedif the tidal volume of successive breaths remains less than the tidalvolume threshold for a period in excess of the duration threshold. Mixedapnea/hypopnea episodes may also occur. In these cases, the period ofdisordered breathing is characterized by shallow breaths ornon-breathing intervals. During the mixed apnea/hypopnea episodes, thetidal volume of each breath remains less than the tidal volume thresholdfor a period exceeding the duration threshold.

Transthoracic impedance is sensed and used to determine the patient'srespiration cycles. Each breath 1710 is characterized by a breathinterval, i.e., the interval of time between two impedance signal maximaand a tidal volume (TV).

If a breath interval exceeds 1715 the duration threshold, then therespiration pattern is consistent with an apnea event, and an apneaevent trigger is turned on 1720. If the tidal volume of the breathinterval exceeds 1725 the tidal volume threshold, then the breathingpattern is characterized by two respiration cycles of normal volumeseparated by a non-breathing interval. This pattern represents a purelyapneic disordered breathing event, and apnea is detected 1730. Becausethe final breath of the breath interval was normal, the apnea eventtrigger is turned off 1732, signaling the end of the disorderedbreathing episode. However, if the tidal volume of the breath intervaldoes not exceed 1725 the tidal volume threshold, the disorderedbreathing period is continuing and the next breath is checked 1710.

If the breath interval does not exceed 1715 the duration threshold, thenthe tidal volume of the breath is checked 1735. If the tidal volume doesnot exceed 1735 the tidal volume threshold, the breathing pattern isconsistent with a hypopnea cycle and a hypopnea event trigger is set on1740. If the tidal volume exceeds the tidal volume threshold, then thebreath is normal.

If a period of disordered breathing is in progress, detection of anormal breath signals the end of the disordered breathing. If disorderedbreathing was previously detected 1745, and if the disordered breathingevent duration has extended for a period of time exceeding 1750 theduration threshold, and the current breath is normal, then thedisordered breathing trigger is turned off 1760. In this situation, theduration of the disordered breathing episode was of sufficient durationto be classified as a disordered breathing episode. If an apnea eventwas previously triggered 1765, then an apnea event is declared 1770. Ifa hypopnea was previously triggered 1765, then a hypopnea event isdeclared 1775.

If disordered breathing was previously detected, but the duration of thedisordered breathing episode did not extend for a period of timeexceeding 1750 the duration threshold, then the period of disorderedbreathing was not of sufficient duration to be classified as adisordered breathing episode 1755.

Although the specific examples of disordered breathing provided aboveinvolve types of disordered breathing that generally occur while aperson is asleep, disordered breathing may also occur while a person isawake. Waking disordered breathing is frequently associated withcompromised cardiopulmonary function caused by congestive heart failure.Examples of the types of disordered breathing that may occur while aperson is awake include, for example, periodic breathing andCheyne-Stokes breathing.

Periodic breathing involves successive periods of regular respirationfollowed by apneic periods. Although periodic breathing is more frequentduring sleep, it can also occur while the patient is awake.Cheyne-Stokes breathing is another example of a wake-disorderedbreathing condition. Cheyne-Stokes breathing is characterized byrhythmic increases and decreases in the tidal volume of breaths andbreathing frequency. Cheyne-Stokes breathing particularly affectspatients who have heart problems, such as congestive heart failure, ornervous disorders, such as those caused by a stroke.

The methods, devices, and systems of the invention described herein areparticularly well-suited for detecting sleep-disordered breathing, suchas apnea and hypopnea. However, the principles of the invention are alsoapplicable to implement detection of disordered breathing episodes thatoccur while the patient is awake. Characteristics of detectedrespiration patterns may be determined and used to detectwake-disordered breathing episodes such as Cheyne-Stokes and periodicbreathing. By the methods of the invention, one or more disorderedbreathing indices indicative of wake-disordered breathing may beestablished and compared with respiration signals to detect episodes ofwake-disordered breathing.

Various modifications and additions can be made to the preferredembodiments discussed hereinabove without departing from the scope ofthe present invention. Accordingly, the scope of the present inventionshould not be limited by the particular embodiments described above, butshould be defined only by the claims set forth below and equivalentsthereof.

1. An implantable medical device, comprising: a respiration sensorconfigured to sense respiration of a patient and to generate arespiration signal; an artifact sensor configured to sense a signalindicative of non-respiration related artifacts and to generate anartifact signal; a disordered breathing detector configured to avoiderroneous detections of disordered breathing based on the artifactsignal, the disordered breathing detector further configured todetermine characteristics of the respiration signal, including at leastdetermining one or both of tidal volumes and breath intervals from therespiration signal, to compare the characteristics of the respirationsignal to one or more respiration metrics, and to detect the disorderedbreathing based on the comparison, the disordered breathing detectorfurther configured to determine characteristics of the disorderedbreathing, including at least an apnea/hypopnea index; a memory coupledto the disordered breathing detector and configured to store thecharacteristics of disordered breathing; and a sleep detector configuredto determine if the patient is awake or asleep based on a sleepthreshold that is adjustable using another sleep-related signal.
 2. Thedevice of claim 1, wherein the sleep threshold is a patient activitythreshold and the other sleep-related signal is a minute ventilationsignal.
 3. An implantable medical device, comprising: a respirationsensor configured to sense respiration of a patient and to generate arespiration signal; an artifact sensor configured to sense a signalindicative of non-respiration related artifacts and to generate anartifact signal; a disordered breathing detector configured to avoiderroneous detections of disordered breathing based on the artifactsignal, the disordered breathing detector further configured todetermine characteristics of the respiration signal, including at leastdetermining one or both of tidal volumes and breath intervals from therespiration signal, to compare the characteristics of the respirationsignal to one or more respiration metrics, and to detect the disorderedbreathing based on the comparison, the disordered breathing detectorfurther configured to determine characteristics of the disorderedbreathing, including at least an apnea/hypopnea index; and a memorycoupled to the disordered breathing detector and configured to store thecharacteristics of disordered breathing; wherein the disorderedbreathing detector is configured to analyze the respiration patternusing the respiration metrics and detect mixed apnea and hypopnea orCheyne Stokes respiration based on the analysis.
 4. An implantablemedical device, comprising: a respiration sensor configured to senserespiration of a patient and to generate a respiration signal; anartifact sensor configured to sense a signal indicative ofnon-respiration related artifacts and to generate an artifact signal; adisordered breathing detector configured to avoid erroneous detectionsof disordered breathing based on the artifact signal, the disorderedbreathing detector further configured to determine characteristics ofthe respiration signal, including at least determining one or both oftidal volumes and breath intervals from the respiration signal, tocompare the characteristics of the respiration signal to one or morerespiration metrics, and to detect the disordered breathing based on thecomparison, the disordered breathing detector further configured todetermine characteristics of the disordered breathing, including atleast an apnea/hypopnea index; and a memory coupled to the disorderedbreathing detector and configured to store the characteristics ofdisordered breathing; wherein the disordered breathing detector isconfigured to discriminate between apnea, hypopnea, and mixed apnea andhypopnea disordered breathing episodes.
 5. An implantable medicaldevice, comprising: a respiration sensor configured to sense respirationof a patient and to generate a respiration signal; an artifact sensorconfigured to sense a signal indicative of non-respiration relatedartifacts and to generate an artifact signal; a disordered breathingdetector configured to avoid erroneous detections of disorderedbreathing based on the artifact signal, the disordered breathingdetector further configured to determine characteristics of therespiration signal, including at least determining one or both of tidalvolumes and breath intervals from the respiration signal, to compare thecharacteristics of the respiration signal to one or more respirationmetrics, and to detect the disordered breathing based on the comparison,the disordered breathing detector further configured to determinecharacteristics of the disordered breathing, including at least anapnea/hypopnea index; and a memory coupled to the disordered breathingdetector and configured to store the characteristics of disorderedbreathing; wherein the disordered breathing detector is configured todetermine a duration of an ongoing disordered breathing episode and todiscriminate between apnea, hypopnea, and mixed apnea and hypopnea ifthe disordered breathing duration exceeds an event duration threshold.6. An implantable medical system, comprising: a respiration sensorconfigured to sense respiration of the patient and generate arespiration signal; a sensor configured to generate a signal indicativeof non-respiration related artifacts; means for avoiding erroneousdetections of disordered breathing based on the sensed artifact signal;means for determining characteristics of the respiration signal,including at least determining one or both of tidal volumes and breathintervals of the respiration signal, comparing the characteristics ofthe respiration signal to one or more respiration metrics, detecting thedisordered breathing based on the comparison, and determiningcharacteristics of the disordered breathing, including at least anapnea/hypopnea index; a memory configured to store the characteristicsof the sleep disordered breathing in the implantable device; and meansfor determining if the patient is asleep based on a sleep threshold thatis adjustable using another sleep-related signal.
 7. An implantablemedical system, comprising: a respiration sensor configured to senserespiration of the patient and generate a respiration signal; a sensorconfigured to generate a signal indicative of non-respiration relatedartifacts; means for avoiding erroneous detections of disorderedbreathing based on the sensed artifact signal; means for determiningcharacteristics of the respiration signal, including at leastdetermining one or both of tidal volumes and breath intervals of therespiration signal, comparing the characteristics of the respirationsignal to one or more respiration metrics, detecting the disorderedbreathing based on the comparison, and determining characteristics ofthe disordered breathing, including at least an apnea/hypopnea index; amemory configured to store the characteristics of the sleep disorderedbreathing in the implantable device; and means for discriminatingbetween apnea, hypopnea, and mixed apnea and hypopnea disorderedbreathing episodes.
 8. An implantable medical system, comprising: arespiration sensor configured to sense respiration of the patient andgenerate a respiration signal; a sensor configured to generate a signalindicative of non-respiration related artifacts; means for avoidingerroneous detections of disordered breathing based on the sensedartifact signal; means for determining characteristics of therespiration signal, including at least determining one or both of tidalvolumes and breath intervals of the respiration signal, comparing thecharacteristics of the respiration signal to one or more respirationmetrics, detecting the disordered breathing based on the comparison, anddetermining characteristics of the disordered breathing, including atleast an apnea/hypopnea index; a memory configured to store thecharacteristics of the sleep disordered breathing in the implantabledevice; means for determining a duration of the disordered breathing;and means for discriminating between apnea, hypopnea, and mixed apneaand hypopnea if the disordered breathing duration exceeds an eventduration threshold.
 9. An implantable medical system, comprising: arespiration sensor configured to sense respiration of the patient andgenerate a respiration signal; a sensor configured to generate a signalindicative of non-respiration related artifacts; means for avoidingerroneous detections of disordered breathing based on the sensedartifact signal; means for determining characteristics of therespiration signal, including at least determining one or both of tidalvolumes and breath intervals of the respiration signal, comparing thecharacteristics of the respiration signal to one or more respirationmetrics, detecting the disordered breathing based on the comparison, anddetermining characteristics of the disordered breathing, including atleast an apnea/hypopnea index; a memory configured to store thecharacteristics of the sleep disordered breathing in the implantabledevice; and sleep detection means for detecting sleep based on aplurality of sleep-related signals and at least a first sleep threshold,the sleep detection means providing a sleep indication to the means fordetermining characteristics of the respiration signal.
 10. The system ofclaim 9, wherein the sleep detection means compares a first signal valuefor one of the sleep-related signals to the first sleep threshold, andadjusts the first sleep threshold based on another of the sleep-relatedsignals.
 11. An implantable medical device, comprising: a respirationsensor configured to sense respiration of a patient and to generate arespiration signal; an artifact sensor configured to sense a signalindicative of non-respiration related artifacts and to generate anartifact signal; a disordered breathing detector configured to avoiderroneous detections of disordered breathing based on the artifactsignal, the disordered breathing detector further configured todetermine characteristics of the respiration signal, including at leastdetermining one or both of tidal volumes and breath intervals from therespiration signal, to compare the characteristics of the respirationsignal to one or more respiration metrics, and to detect the disorderedbreathing based on the comparison, the disordered breathing detectorfurther configured to determine characteristics of the disorderedbreathing, including at least an apnea/hypopnea index; a memory coupledto the disordered breathing detector and configured to store thecharacteristics of disordered breathing; and a sleep detector configuredto determine the patient's sleep status based on a plurality ofsleep-related signals and at least a first sleep threshold, the sleepdetector providing the determined sleep status to the disorderedbreathing detector.
 12. The device of claim 11, wherein the sleepdetector is configured to compare a first signal value for one of thesleep-related signals to the first sleep threshold, and wherein thesleep detector is further configured to adjust the first sleep thresholdbased on another of the sleep-related signals.
 13. The device of claim12, wherein the plurality of sleep-related signals comprise anaccelerometer signal and the respiration signal.